Proefschrift Rijksuniversiteit Groningen. / Met lit.opg.

The rate of anaerobic digestion (AD) often depends on the rate-limiting hydrolysis step that makes organics available to microorganisms. To achieve efficient conversion of particulates to soluble materials and finally methane, the biomass in the digester must be provided with optimal operational conditions that will allow for biomass retention and substrate metabolism. Two approaches were employed in this study to improve the ultimate biodegradability of waste activated sludge (WAS) - Pre-treatment (PT) and operation using an Anaerobic Membrane Bioreactor (AnMBR). PT of WAS is one way of speeding up hydrolysis. It has been proposed that PT leads to the lysis of cells, which in turn causes the release and solubilisation, and thus availability of intracellular matter to microorganisms for microbial growth and metabolic activities. This study compared the effect of thermal, sonication, and sonication + hydrogen peroxide PT on chemical oxygen demand (COD) solubilisation of WAS. Based on the soluble COD (SCOD) release, it was concluded that combined chemi-sonic treatment resulted in better WAS degradation rather than individual ultrasonic pre-treatment and thermal PT. The highest solubilisation rate was observed at a chemi-sonic PT of 50gH2O2/kgTS and sonication duration of 60 minutes. At this PT, a COD solubilisation of 40% was observed which was significantly different than PT involving only sonication and no pre-treatment (0.88%) at 95% confidence. Therefore a peroxide-sonic PT was chosen to treat WAS in this study as it was expected to result in the greatest improvement in WAS biodegradability. In addition to PT, biodegradability of WAS can also be improved by coupling PT with an AnMBR. AnMBRs prevent biomass washout by decoupling the solids retention time (SRT) from the hydraulic retention time (HRT). Thus, a long SRT can be used to provide sufficient duration for biological activities without increasing the volume of the reactor. In this study, a 4.5L AnMBR with an HRT and SRT of 3 and 20 days, respectively was used to treat raw and PT WAS. In order to compare the biodegradability of PT and raw WAS, the AnMBR was operated in three phases. Phase 1 was operated with raw WAS, Phase 2 was operated with WAS pre-treated with 50 gH2O2/kgTS and 20 minutes ultrasound (US), and Phase 3 was operated with WAS pre-treated with 50 gH2O2/kgTS and 60 minutes US. The anaerobic biodegradability of WAS following a combination of ultrasonic pre-treatment and H2O2 addition was significantly improved, with Phase 3 resulting in the greatest improvement. The COD destruction for phases 1, 2, and 3 were 49%, 58%, and 63%, respectively whereas the volatile suspended solids (VSS) destruction for phases 1, 2, and 3 were 46%, 71%, and 77% respectively. Organic Nitrogen (Org-N) destruction increased from 44% to 52% for phases 1 and 2 respectively. A further increase of 18% in Org-N destruction was observed in phase 3. This improvement in biodegradability of WAS was attributed to the high solubilisations of COD, VSS, and ON and conversion of non-biodegradable materials to biodegradable fractions. In order to determine the effect of PT of WAS on membrane performance, the transmembrane pressure (TMP) and fouling rate were monitored throughout the operation of the AnMBR. Negligible variation in membrane performance was observed over all three phases. At a constant low flux of 2.75 litres/m2/hour (LMH), the TMP and the fouling rate remained low over the course of operation. In order to maintain the performance of the membrane, maintenance cleaning with 50 ml of 2g/L critic acid solution followed by 50 ml of 0.2 g/L sodium hypochlorite was performed three times a week. In addition, a gas sparing rate of 2 L/minute and a permeation cycle of 10 minutes with 8 minutes of operation followed by 2 minutes of relaxation was employed. During phase 2 of this study, a new membrane was installed due to a faulty gas sparging pump. A slight decrease of TMP was observed with the installation of the new membrane; however the decrease was minimal. In addition critical flux for phases 2 and 3 were determined to be in the range of 6 to 12 LMH. In conclusion, the incorporation of H2O2-US PT with AD could allow treatment plants to substantially reduce the mass flow of solids and organics and thus result in a decrease in requirements for downstream sludge processing. With sufficient maintenance, steady operation could be achieved for a hollow fibre AnMBR with a total solids concentration range of 20-25 g/L, an HRT of 3 days, and an SRT of 20 days. It was found that PT could be successfully integrated with AnMBR to substantially reduce the HRT required for digestion when compared to conventional designs.

HT biomass sonicated at ES inputs < 56KJ/gTS decreased floc size by 41% and enhanced its metabolic activity by 50-250% compared to control. ES inputs >118 KJ/gTS caused HT biomass solubilization and irreversible loss of its metabolic activity and reflocculation ability. During continuous activated sludge processing (ASP) of real primary effluent the observed yield (Yobs) decreased by 20% compared to control ASP at SF (stress factor) of 1 (biomass exchanged without USPT). At SF of 0.5, 1 and 1.5 (biomass exchanged with USPT) the Yobs further decreased by 33, 25 and 44% respectively as compared to control. This indicated that combining biomass anoxic exposure with USPT enhanced sludge reduction by increasing microbial maintenance metabolism likely in combination with microbial flora shift in the ASP depending on SF.

HT biomass sonicated at ES inputs < 56KJ/gTS decreased floc size by 41% and enhanced its metabolic activity by 50-250% compared to control. ES inputs >118 KJ/gTS caused HT biomass solubilization and irreversible loss of its metabolic activity and reflocculation ability. During continuous activated sludge processing (ASP) of real primary effluent the observed yield (Yobs) decreased by 20% compared to control ASP at SF (stress factor) of 1 (biomass exchanged without USPT). At SF of 0.5, 1 and 1.5 (biomass exchanged with USPT) the Yobs further decreased by 33, 25 and 44% respectively as compared to control. This indicated that combining biomass anoxic exposure with USPT enhanced sludge reduction by increasing microbial maintenance metabolism likely in combination with microbial flora shift in the ASP depending on SF.

Zugl.: Tromsø, Univ., Diss., 2007.

Submitted by Pós Imunologia (ppgimicsufba@gmail.com) on 2017-02-07T18:45:00Z No. of bitstreams: 1 TESE_CINTIA MARQUES.pdf: 774112 bytes, checksum: 4eb77463eb7b53260c945d76b45ec8f9 (MD5) / Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2017-02-08T16:17:19Z (GMT) No. of bitstreams: 1 TESE_CINTIA MARQUES.pdf: 774112 bytes, checksum: 4eb77463eb7b53260c945d76b45ec8f9 (MD5) / Made available in DSpace on 2017-02-08T16:17:19Z (GMT). No. of bitstreams: 1 TESE_CINTIA MARQUES.pdf: 774112 bytes, checksum: 4eb77463eb7b53260c945d76b45ec8f9 (MD5) / CAPES / Asma e atopia são condições determinadas por fatores genéticos e ambientais, que podem atuar tanto independentemente quanto em interação. Diversos estudos de associação ampla do genoma têm sido desenvolvidos para tentar compreender quais componentes genéticos influenciam na asma. No entanto, genes localizados no cromossomo X são frequentemente pouco representados. Um dos genes localizados nesse cromossomo, o FOXP3, codifica uma fator de transcrição que está diretamente relacionado à ativação e diferenciação de células T regulatórias. Tais células constituem um importante mecanismo relacionado ao controle de doenças alérgicas. Diversos polimorfismos já foram descritos nas regiões codificante e regulatória do FOXP3, o que sugere que os mesmos possam ter um impacto funcional sobre a proteína correspondente. Desta forma, fatores genéticos que afetam o gene FOXP3 podem determinar diferenças na susceptibilidade a doenças alérgicas, tais como a asma. Neste contexto, o presente trabalho teve como objetivo avaliar o impacto de polimorfismos em genes localizados no cromossomo X, a exemplo FOXP3, no desenvolvimento da asma e atopia. Para analisar a associação de polimorfismos presentes no cromossomo X e asma, foi realizado um X-WAS (Estudo da Associação Ampla do Cromossomo X). Já para verificar a associação de polimorfismos no gene FOXP3 com asma e atopia foi realizado um estudo de gene-candidato. Como resultados mais importantes destaca-se a associação do polimorfismo rs12007907 no gene IL1RAPL com sintomas de asma (P = 3.33x10-6; OR=0.49, 95% IC= 0.37 - 0.67) e níveis de produção de IL-13 (p = 0.045) no X-WAS; a associação dos polimorfismos no gene FOXP3 rs2232368 (OR = 1,95; 95% IC= 1.04 – 3,66) com sintomas de asma, rs2232368 (OR = 2,31; 95% IC= 1,16 – 4,59), rs3761549 (OR = 1,44; 95% IC= 1,028 – 2,018) e rs2280883 (OR = 0,836; 95% IC= 0,704 – 0,992) com atopia, além da interação entre o rs2280883 no FOXP3 e infecção com EBV no desenvolvimento de atopia definida por SPT (OR = 0,64; 95% IC: 0,47 – 0,87) e IgE específico para aeroalérgenos (OR = 0,62; 95% IC: 0,46 – 0,83). Estes achados sugerem que polimorfismos em genes do cromossomo X, dentre eles FOXP3 e IL1RAPL, possuem impacto no desenvolvimento de asma e alergia em nossa população. No entanto, novos estudos devem ser conduzidos na tentativa de elucidar melhor o impacto funcional destes polimorfismos aqui descritos no desenvolvimento de asma e alergia, além da replicação em outras populações. / Asthma and atopy are conditions determined by genetic and environmental factors, which can act independently and in interaction. Several Genome Wide Association Studies has been conducted to try to understand which genetic components influence asthma. However, genes located on the X chromosome are often underrepresented. One of the genes located in this chromosome, the FOXP3, encodes a transcription factor that is directly related to the activation and differentiation of regulatory T cells. Such cells are an important mechanism related to the control of allergic diseases. Several polymorphisms have been described in coding and regulatory regions of the FOXP3, which suggests that they may have a functional impact on the corresponding protein. Thus, genetic factors affecting the FOXP3 gene can determine differences in susceptibility to allergic diseases such as asthma. In this context, this study aimed to assess the impact of polymorphisms in genes located on the X chromosome, such the FOXP3, in the asthma and atopy risk. To analyze the association between polymorphisms on chromosome X and asthma, it was carried out an X-WAS (Study of Wide Association of Chromosome X). To verify the association of polymorphisms in the FOXP3 gene with asthma and atopy, a gene-candidate study was conducted. The meaningful results were the association of rs12007907 polymorphism in IL1RAPL gene with asthma symptoms (p = 3.33x10-6; OR = 0.49, 95% CI = 0.37 - 0.67) and IL-13 production levels (p = 0.045) in X-WAS; furthermore we observed association of rs2232368 in the FOXP3 gene with asthma symptoms (OR = 1.95; 95% CI = 4.1 - 3.66) and a association with atopy for the rs2232368 (OR = 2.313; 95% CI = 1.16 to 4.59), the rs3761549 (OR = 1.44; 95% CI = 1.03 to 2.02) and rs2280883 (OR = 0.836, 95% CI = 0.70 to 0.99). In addition, we reported an interaction between the rs2280883 located on FOXP3 and infection with EBV in the atopy development defined by SPT (OR = 0.64; 95% CI: 0.47 - 0.87) and specifc IgE to allergens (OR = 0.62; 95% CI: 0.46 - 0.83). These findings suggest that polymorphisms in genes of the X chromosome, including FOXP3 and IL1RAPL, have potential impact on the development of asthma and allergy in our population. However, further studies should be conducted to elucidate the functional impact of these polymorphisms described in this study in the asthma and atopy, as well as replication in other populations.

No description available.

HT biomass sonicated at ES inputs < 56KJ/gTS decreased floc size by 41% and enhanced its metabolic activity by 50-250% compared to control. ES inputs >118 KJ/gTS caused HT biomass solubilization and irreversible loss of its metabolic activity and reflocculation ability. During continuous activated sludge processing (ASP) of real primary effluent the observed yield (Yobs) decreased by 20% compared to control ASP at SF (stress factor) of 1 (biomass exchanged without USPT). At SF of 0.5, 1 and 1.5 (biomass exchanged with USPT) the Yobs further decreased by 33, 25 and 44% respectively as compared to control. This indicated that combining biomass anoxic exposure with USPT enhanced sludge reduction by increasing microbial maintenance metabolism likely in combination with microbial flora shift in the ASP depending on SF.

No description available.

Le syndrome de l’intestin irritable (SII) est un trouble fonctionnel d’origine multifactorielle, impliquant des facteurs environnementaux tels que le stress, l’alimentation et met en jeu un dysfonctionnement de l’axe intestin-cerveau, une micro-inflammation, une dysbiose et une hyperperméabilité intestinale. Le rôle du protéasome dans la régulation de la barrière intestinale au cours du SII a été étudié. De plus, ces troubles fonctionnels intestinaux (TFI) ont également été décrits comme exacerbés chez des patients souffrant d’obésité, dont la physiopathologie est complexe. Néanmoins, les mécanismes impliqués dans cette association restent mal compris et ont donc été recherchés. Dans ce travail, des modèles murins « SII-like » comme le modèle de stress « water avoidance stress » ou WAS et le modèle post-inflammatoire « post-TNBS » ont été utilisés afin d’étudier l’impact d’une inhibition du protéasome sur la régulation de la perméabilité intestinale. L’inhibition pharmacologique du protéasome par le PR-957 ou l’utilisation de souris invalidées pour une sous unité β2i du protéasome limite l’hyperperméabilité intestinale. Une supplémentation orale en glutamine permet également de diminuer la perméabilité intestinale. Une étude protéomique au niveau colique des souris WAS et une étude de l’ubiquitome colique de patients souffrant de SII à profil diarrhéique confirment l’implication du protéasome dans la physiopathologie du SII. Nous avons ensuite cherché à comprendre le lien entre l’obésité et le SII en combinant des modèles d’obésité (génétique et induite par une alimentation riche en graisses ou HFD) et le modèle WAS. Seules les souris HFD présentent une exacerbation de l’hyperperméabilité intestinale et une corticostéronémie plasmatique élevée en réponse au modèle WAS. Des études complémentaires suggèrent que ces résultats sont indépendants de la leptine, de la glycémie et du microbiote intestinal. Nos travaux proposent donc de nouvelles pistes de prise en charge des patients souffrant de SII, par intervention nutritionnelle via la glutamine ou en utilisant le protéasome comme cible thérapeutique. Nous suggérons également un rôle de l’alimentation (riche en graisse) dans le développement des TFI au cours de l’obésité. / Irritable bowel syndrome (IBS) is a multifactorial functional disorder, involving environmental factors (stress and diet for instance), gut-brain-axis dysfunction, micro-inflammation, dysbiosis and an alteration of intestinal permeability. The role of the proteasome in the regulation of the intestinal barrier during IBS has been studied. In addition, these intestinal functional disorders have also been described in patients with obesity. Nevertheless, the mechanisms underlying an association of intestinal functional disorders in the obesity context, remain poorly understood and have therefore been investigated in this thesis. In this study, "IBS-like" mouse models such as water avoidance stress (WAS) and the post-inflammatory (post-TNBS) models, were used to study the impact of proteasome inhibition on the regulation of intestinal permeability. We found that the pharmacological inhibition of the proteasome (with PR-957) or the use of knock-out mice for a subunit of the proteasome (β2i -/-) limit intestinal hyperpermeability occured in IBS-Like models. Moreover, we found that oral supplementation with glutamine also reduces intestinal hyperpermeability, wich, thus, can be considered as a putative nutritional treatment for IBS. A colonic proteomic study of WAS mice and a study of colonic ubiquitoma in IBS patients with diarrheal profiles confirmed the involvement of proteasome in the pathophysiology of IBS. Therefore, the link between obesity and IBS was examined by combining models of obesity (ob/ob genetic and high-fat diet [HFD] models) with WAS model. Only HFD mice displayed enhanced intestinal hyperpermeability and higher plasma corticosterone levels in response to WAS. Further studies suggest that these results, themselve, are independent of leptin, glycaemia and gut microbiota. This study paves new ways of treating patients suffering from IBS, by nutritional intervention via glutamine or by using the proteasome as a therapeutic target. We also suggest a role of diet (high fat) in the development of intestinal functional disorders during obesity.